Leishmaniasis, caused by the most-genetically diverse intracellular protozoan parasite, is exemplified by its diversity and complexity. Visceral leishmaniasis (VL), also known as Kala-azar, is caused by members of L. donovani (LD) complex resulting in clinical symptoms like fever, cachexia, hepatosplenomegaly, and blood cytopenia. Active VL is associated with the absence of parasite specific cell mediated immune response. Carvalho, E. M., et al. Infect. Immun. 33:498. (1981); Carvalho, E. M. et al., A J. Clin. Invest. 76:2066. (1985). VL has also been increasingly recognized as an opportunistic infection in individuals infected with HIV virus. Pintado et al. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study, Medicine (Baltimore); 80:54 (2001). The WHO has identified leishmaniasis as a major and increasing public health problem. United Nations Development Program/World Bank/World Health Organization, The Leishmaniasis. WHO Special Program for Research and Training in Tropical Diseases. Ninth Program Report. Tropical diseases: progress in international research, 1987-1988 (1989). Visceral form of leishmaniasis is fatal if left untreated with recent epidemics in Sudan and India resulting in more than 100000 deaths. Melby, P. C., et al., Infect. Immun. 68: 5595 (2000).
Failure of the pentavalent antimonials, presently the main form of chemotherapeutic treatment worldwide, is attributed to the emergence of antimony resistant Leishmania strains resulting in frequent relapses after treatment. Kafetzis, et al. Curr. Opin. Infect. Dis. 15:289 (2002); Murray, H. W., Antimicrob. Agents Chemother. 45:2185 (2001). In India, antimony is no longer useful as a drug as 65% of VL patients fail to respond or promptly relapse Sundar, S., D, et al. Clin. Infect. Dis. 31:1104 (2000). Alternative chemotherapeutic treatments with amphotericin B and its lipid formulation have severe limitations due to toxic effect and prohibitive high cost of treatment Murray, H. W., Antimicrob. Agents Chemother: 45:2185 (2001). An in vitro study has shown that Leishmania also developed resistance against Miltefosine, a recently approved effective oral drug for treatment of VL. Perez-Victoria, Antimicrob. Agents Chemother. 45(9): 2468 (2001). Growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine strategy against VL deepens the crisis.
Accordingly, there is a need for a vaccine as a possible prophylactic approach against visceral Leishmaniasis.